The overall objective of this project is to determine the clinical significance of changes in Fletcher factor or prekallikrein in man. Fletcher factor (prekallikrein, PK) is now proposed to be the pivotal factor in the Hageman factor-dependent reactions, i.e., fibrinolysis, neutrophil chemotaxis, kinin sytem, and the intrinsic coagulation system. Two basic questions will be addressed: (a) will determination of levels of PK in conditions such as renal disease, intravascular coagulation, inflammatory diseases, in neonatal disease, allergic disorders provide diagnostic or prognostic help or help us in our basic understanding of triggering mechanisms, and (b) what is the significance of total deficiency of prekallikrein in man as studied in individuals with Fletcher factor deficiency.